Primary infection with varicella-zoster virus (VZV) causes chickenpox, and reactivation of the virus from latency results in zoster. The goals of this project are to identify and determine the function of VZV genes that are expressed during active infection and during latency in the body. VZV genes that are expressed during active infection and regulate viral gene expression in vitro are being studied. VZV encodes five proteins (ORF4, 10, 61, 62, 63) that regulate expression of other VZV genes in vitro. A transcriptional activation domain in the VZV ORF10 protein was identified. Using a computer program (hydrophobic cluster analysis) we were able to identify domains in other herpesviruses that can also activate transcription. The VZV ORF10 protein was shown to interact with two cellular proteins (Oct1, HCF). This interaction allows the ORF10 protein to activate transcription of VZV ORF62. An additional cellular protein (NF-Y) was shown to regulate the expression of ORF62 protein. Analysis of central nervous system tissues from human cadavers without active evidence of VZV infection indicates that at least two VZV genes (ORF29 and ORF62) are expressed while the virus is latent in the central nervous system. Two chimpanzees inoculated with VZV developed a papular rash 10 days after inoculation. VZV DNA was detected in white blood cells of both animals shortly after inoculation and in a skin biopsy from one of the animals at the time of the rash.